Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes
Deletion of master regulators of the B cell lineage reprograms B cells into T cells. Here we found that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is not present in cells committed to the B cell or T cell lineage, was able to reprogram pro-pre-B cells into functional early T cell lineage progenitors. This reprogramming started in the bone marrow and was completed in the thymus and gave rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immunological functions that closely resembled those of their natural counterparts. Hoxb5 repressed B cell ‘master genes’, activated regulators of T cells and regulated crucial chromatin modifiers in pro-pre-B cells and ultimately drove the B cell fate-to-T cell fate conversion. Our results provide a de novo paradigm for the generation of functional T cells through reprogramming in vivo.
Authors: Zhang M, Dong Y, Hu F, Yang D, Zhao Q, Lv C, Wang Y, Xia C, Weng Q, Liu X, Li C, Zhou P, Wang T, Guan Y, Guo R, Liu L, Geng Y, Wu H, Du J, Hu Z, Xu S, Chen J, He A, Liu B, Wang D, Yang YG, Wang J.
Influence Factor: 21.506
Citation: Nat Immunol 19, 279-290 (2018).